Biology subjects

Kollar, A.

Publications and source records attributed to Kollar, A..

3 recordsLinked to original sources

bioRxiv2026

Physiological load via voluntary wheel running maintains Achilles tendon homeostasis by region-specific cellular responses

Physiological load is vital for maintaining tendon homeostasis, preserving the organized extracellular matrix that enables tendons to withstand extreme forces. Although tenocytes are regarded as the primary regulators of extracellular matrix production, precisely how cells facilitate the maintenance of homeostasis in response to physiological load is poorly understood. Here, we used Voluntary Wheel Running (VWR) as a model of physiological load to delineate the specific cellular contributions to mouse Achilles tendon homeostasis. Eight weeks of VWR led to a smaller cross-sectional area, increased mechanical and material properties at the midsubstance, which corresponded to a decreased proportion of small (0-60 nm) collagen fibrils and an increased proportion of larger (100-60 nm) collagen fibrils compared to sedentary controls. Using Visium HD spatial transcriptomics, we identified region-specific cell clusters (insertion vs. midsubstance). In response to physiological load, cells in the insertion and midsubstance upregulate distinct genes that reinforce the fibrocartilage interface and collagen-rich tendon matrix, respectively. Notably, Clu, Myoc, and Ccdc80 were upregulated with VWR in the midsubstance, with previously uncharacterized roles in tendon homeostasis. Together, our findings suggest that in response to physiological load, tendon cells maintain homeostasis by region-specific responses. Given that insertional and midsubstance tendinopathy is function-limiting and painful, defining the region-specific cellular responses will be key to advancing therapeutic prospects for tendon health. New and NoteworthyThis study is the first spatially rigorous characterization of the tendon response to physiological load using a Voluntary Wheel Running (VWR) model. VWR led to smaller, stronger, but not stiffer tendons at the midsubstance compared to sedentary controls. This corresponded with significant decreased proportion of small collagen fibrils and a shift toward an increased proportion of large collagen fibrils. Using Visium HD spatial transcriptomics, we identified region-specific transcriptional responses to physiological load that maintain homeostasis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/722285v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@13aa717org.highwire.dtl.DTLVardef@1afe3f1org.highwire.dtl.DTLVardef@9e1137org.highwire.dtl.DTLVardef@17c47bc_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Establishment of a Mycoplasma hyorhinis challenge model in five-week-old piglets

Mycoplasma hyorhinis is an emerging swine pathogen bacterium with high prevalence worldwide. The main lesions caused are arthritis and polyserositis and the clinical manifestation of the disease may result in significant economic losses due to the decreased weight gain and enhanced medical costs. Our aim was to compare two challenge routes to induce M. hyorhinis infection using the same clinical isolate. Five-week-old, Choice hybrid pigs were inoculated on two consecutive days by intravenous route (Group IV-IV) or by intravenous and intraperitoneal route (Group IV-IP). Mock infected animals were used as control (Control Group). After challenge, the clinical signs were recorded for 28 days, after which the animals were euthanized. Gross pathological and histopathological examinations, PCR detection, isolation and genotyping of the re-isolated Mycoplasma sp. and culture of bacteria other than Mycoplasma sp. were carried out. ELISA test was used to detect anti-M. hyorhinis immunoglobulins in the sera of all animals. Pericarditis and polyarthritis were observed in both challenge groups, however the serositis was more severe in Group IV-IV. Statistically significant differences were detected between the challenged groups and the control group regarding the average daily weight gain, pathological scores and ELISA titres. Additionally, histopathological scores in Group IV-IV differed significantly from the scores in the Control Group. All re-isolated strains were the same or a close genetic variant of the original challenge strain. Our results indicate that both challenge routes are suitable for modelling the disease. However, due to the more severe pathological lesions and the more natural-like route of infection in Group IV-IV, the two-dose intravenous challenge is recommended by the authors to induce serositis and arthritis associated with M. hyorhinis infection.

microbiology↗

bioRxiv2022

Patient-derived tumoroids of advanced high-grade neuroendocrine neoplasms mimic patient chemotherapy responses and guide the design of personalized combination therapies

There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous epithelial malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced high-grade GEP-NEN patients and applied this model for targeted rapid ex vivo pharmacotyping, next-generation sequencing, and perturbational profiling. We used tissue-matched PD tumoroids to profile individual patients, compared ex vivo drug response to patients clinical response to chemotherapy, and investigated treatment-induced adaptive stress responses. PD tumoroids recapitulated biological key features of high-grade GEP-NEN and mimicked clinical response to cisplatin and temozolomide ex vivo. When we investigated treatment-induced adaptive stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5A and interferon-beta, which act synergistically in combination with cisplatin. Since ex vivo drug response in PD tumoroids matched clinical patient responses to standard-of-care chemotherapeutics for GEP-NEN, our rapid and functional precision oncology approach could expand personalized therapeutic options for patients with advanced high-grade GEP-NEN.

cancer biology↗